Q: What is the difference between the RDRC and a SHUR application?
An application involving the administration of radioactive materials (radio drugs) to a human research subject for the basic research of advancing scientific knowledge. The research is intended to obtain basic information regarding the metabolism of radioactive drugs including kinetics, distribution, dosimetry, and localization ... or ... obtain basic information regarding human physiology, pathophysiology, and biochemistry of radioactive drugs.
An RDRC research application is not intended to determine the safety and effectiveness of a radioactive drug in human subjects as a therapy, diagnostic, or preventive medical product. The research is not intended for the immediate therapeutic, diagnostic, or preventive benefit to the human research study subject and is not designed to involve the routine medical management of clinical patients.
Example of a RDRC Study: ‘An investigator wants to study the expression of a specific neurotransmitter receptor in the brain.’
RDRC research applications can involve human research protocols involving radioactive drugs without either: (1) a New Drug Application (NDA), (2) an approved Investigational New Drug (IND) application, or (3) an IND Exemption. Any human research subject protocol submitted to the RDRC is also required to receive Institutional Review Board (IRBMED) approval. IRBMED approval is contingent upon RDRC review and approval. Any revisions or modifications required by the RDRC must be incorporated into the protocol before final, full approval by the IRBMED will be granted.
An application involving the clinical administration of radioactive materials (radioactive drugs) for routine medical patients or the administration of radioactive drugs to human research subjects involving (1) FDA-approved New Drug Applications (NDA), (2) FDA-approved Investigational New Drugs (IND), or (3) FDA-approved IND Exemptions.
A SHUR application can involve the clinical administration of radiopharmaceuticals intended for therapeutic use, diagnostic use, or similar purposes or to determine the safety and effectiveness of a drug (clinical trials).
Example of a SHUR Study: 'An investigator wants to study a new radioligand to monitor the treatment response of a brain tumor.'
Any human research subject protocol submitted to the SHUR is also required to receive Institutional Review Board (IRBMED) approval. IRBMED approval is contingent upon RDRC review and approval. Any revisions or modifications required by the SHUR must be incorporated into the protocol before final, full approval by the IRBMED will be granted.
Q: What is the maximum allowed human dosimetry per year per human research subject?
A1: RDRC PROTOCOLS (FDA Regulatory Limits – 21 CFR 361.1)
--- smallest dose with which it is practical to perform the study without jeopardizing the benefits to be obtained from the study.
--- when determining the total radiation doses (effective dose) and dose commitments, the following must be considered:
(1) All radioactive material included in the radioactive drug either as essential material or as significant contaminant or impurity
(2) X-ray procedures that are part of the research study
(3) Possibility of follow-up studies
--- under no circumstances may the radiation dose to an adult research subject from a single study or cumulatively from a number of studies conducted within 1-year be generally recognized as safe if such dose exceeds the following
Whole Body / Active Blood-Forming Organs / Lens of Eye / Gonads (FDA Limits)
Single Dose (Effective Dose) = 3 rem (0.03 Sv)
Annual & Total Effective Dose Commitment = 5 rem (0.05 Sv)
Single Dose = 5 rem (0.05 Sv)
Annual and Total Dose Commitment = 15 rem (0.15 Sv)
A2: SHUR PROTOCOLS (No Stated Limits)
--- there are no stated regulatory dose limits for SHUR applications; however, the SHUR will evaluate each research study for safety on a case-by-case basis.
Q: Can I exceed the maximum allowed number of subjects?
A1: RDRC PROTOCOLS
--- YES.... however, a Principal Investigator must never study more than the maximum number of research subjects approved by the RDRC. For example, if the RDRC approved a research protocol for n=20 subjects, the PI or study group must not exceed n=20 without first seeking and obtaining approval from the RDRC.
--- in addition, RDRC studies must never exceed the FDA limit of 30 research subjects (21 CFR 361.1) without prior approval by the RDRC.
Special Note - multi-arm study protocols may have a different number of approved research subjects authorized by the IRBMED for the ‘total’ protocol; however, there may be a more limited RDRC or SHUR approval for research subjects undergoing a research procedure with administration of a radiopharmaceutical. Thus, the IRBMED ‘maximum’ number of approved research subjects may not be the same maximum number approved by the RDRC/SHUR.
--- at any time a RDRC proposal is approved which intends to involve the exposure of more than 30 research subjects, the Principal Investigator must notify the U-M RDRC/SHUR in advance of exceeding the approved 30 research subjects, complete and submit to the RDRC/SHUR a FDA Form-2915 and justification cover-letter, and the RDRC/SHUR must approve the request and submit to the FDA.
A2: SHUR PROTOCOLS
--- there is no limit on the number of research subjects allowed for a given SHUR study. However, the SHUR will evaluate the number of requested research subjects and determine if the number appears appropriate for the study.
Questions for the RDRC and SHUR committees may be emailed to OSEHRadSafety@umich.edu.